Effect of Shenfu injection on intestinal mucosal barrier in a rat model of sepsis

Wan, Wei; Jiang, Ronglin; Wang, Lingcong; Shu, Lei; Xing, Xi; Zhi, Yuxiang; Wu, Jian; Wu, Yanchun; Zhu, Mingyu; Huang, Liquan

doi:10.1016/j.ajem.2015.01.056

Cited by 18 publications

(11 citation statements)

References 24 publications

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“…Clinically effective treatment schemes are not highlighted, resulting in high morbidity and mortality of enterogenic sepsis. Therefore, how to prevent and cure sepsis-induced intestinal mucosal barrier injury is still a major problem in clinical treatment of sepsis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Curcumin Improved Intestinal Epithelial Barrier Integrity by Up-Regulating ZO-1/Occludin/Claudin-1 in Septic Rats

Liu

Zhu

2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To investigate the protective effect and mechanism of curcumin on intestinal barrier function in rats with enterogenic sepsis. Methods. Rats were divided into Sham group (Sham), Model group (Model), low-dose curcumin group (100 mg/kg), and high-dose curcumin group (200 mg/kg), with 10 rats in each group. Sepsis model was established in model group, low-dose curcumin group, and high-dose curcumin group. After drug intervention, hematoxylin-eosin (HE) staining was used to observe the histopathological changes of small intestine in each group. The levels of TNF-α, IL-1β, and IL-6 in serum and intestinal tissues of rats were determined by ELISA. The expression of ZO-1, occludin, and claudin-1 in ileum was detected by QRT-PCR and Western blot. Western blotting was used to detect the expression of ERK/JNK signaling pathway, NF-κB p65, apoptosis-related proteins Caspase-3, and TNF-α in rat intestinal tissues. Results. HE staining showed that curcumin treatment reduced epithelial cell shedding, interstitial edema, and apoptosis. Compared with model group, DAO activity, serum intestinal fatty acid binding protein (I-FABP), TNF-α, IL-6, and IL-1β expression in curcumin group were decreased in a dose-dependent manner. Curcumin can upregulate the mRNA and protein expression levels of ZO-1, occludin, and claudin-1 in ileum of CLP-induced rats. In addition, curcumin inhibits NF-κB p65 activation and apoptosis by regulating ERK/JNK signaling pathway. Conclusion. Curcumin can reduce inflammatory response and upregulate the expression of intestinal tight junction proteins ZO-1, occludin, and claudin-1 in rats with enterogenic sepsis, and protect intestinal barrier function.

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Section: Discussionmentioning

confidence: 99%

Curcumin Improved Intestinal Epithelial Barrier Integrity by Up-Regulating ZO-1/Occludin/Claudin-1 in Septic Rats

Liu

Zhu

2022

Evidence-Based Complementary and Alternative Medicine

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“…A total of 48 male Sprague-Dawley (SD) rats (weighing 200 ± 20 g) provided by Experimental Animal Center of Lanzhou University Medical College were raised in separate cages, with free access to food and water. The rats were randomly grouped: 12 rats were fed a normal diet until the sampling as normal control group; 12 rats were selected as sham-operated group (abdominal cavity was immediately opened and sutured without ligation and puncture); the remaining rats were subjected to abdominal infection by cecal ligation and puncture (CLP) to induce a rat model of sepsis as previously described (15). In details, the rats were anesthetized by intraperitoneal injection of 2% ketamine hydrochloride (40 mg/kg), fixed in supine position, and their hair on the neck and abdomen was shaved, followed by disinfection with 0.1% benzalkonium bromide.…”

Section: Animal Model Establishmentmentioning

confidence: 99%

Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1

Dou

Zhang

et al. 2021

Front. Immunol.

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Intestinal barrier dysfunction is an important contributor to morbidity caused by sepsis. This study investigates the molecular mechanism by which Ghrelin affects intestinal dysfunction in rat model of sepsis. A rat model of sepsis was established by cecal ligation and puncture (CLP), revealing that Ghrelin was downregulated when sepsis occurs. Increases in the levels of inflammatory factors tumor necrosis factor α (TNF-α), interleukin-1 (IL-1β), IL-6, gastrin, γ-H2AX and 8-OHdG was also detected in this model system, as was an overall increase in oxidative stress. Introduction of exogenous Ghrelin inhibited these increases in inflammatory response and oxidative stress, leading to a reduction of overall sepsis-induced intestinal dysfunction. Ghrelin was then shown to activate SIRT1 expression in vitro, while SIRT1 was found to co-express with KLF4, which in turn was predicted to bind to matrix metalloproteinase 2 (MMP2) promoter. Finally, gain- and loss-of-function experiment demonstrated that SIRT1 upregulated the expression of KLF4 to downregulate MMP2. Collectively, Ghrelin inhibits the oxidative stress and intestinal dysfunction to attenuate sepsis by activating SIRT1 and regulating a KLF4/MMP2 regulatory axis.

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“…The levels of several biomarkers (TNF-α, the ileal malondialdehyde level, the apoptosis index for ileal mucosal epithelial cells, and the Bax protein level) were significantly higher in the CLP group than in the sham group (p < 0.01 or p < 0.05), while some others (the serum level of IL-10, Bcl-2/Bax ratio, Bcl-2 protein level, and occludin protein level) were significantly lower. Both low-dose (5 mL/kg) and high-dose (10 mL/kg) SF significantly ameliorated these changes (p < 0.01 or p < 0.05) in a dose-dependent manner [162]. SF also dose-dependently prevented MAP drop, relieved lung damage, and increased the survival rate in the rat model of endotoxin shock, perhaps through inhibiting the high-mobility group protein B1 (HMGB1)-nuclear factor κB (NF-κB) pathway, thus preventing a cytokine storm [163].…”

Section: Shenfu Injectionmentioning

confidence: 91%

Research Progress in Chinese Herbal Medicines for Treatment of Sepsis: Pharmacological Action, Phytochemistry, and Pharmacokinetics

Cheng

2021

IJMS

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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection; the pathophysiology of sepsis is complex. The incidence of sepsis is steadily increasing, with worldwide mortality ranging between 30% and 50%. Current treatment approaches mainly rely on the timely and appropriate administration of antimicrobials and supportive therapies, but the search for pharmacotherapies modulating the host response has been unsuccessful. Chinese herbal medicines, i.e., Chinese patent medicines, Chinese herbal prescriptions, and single Chinese herbs, play an important role in the treatment of sepsis through multicomponent, multipathway, and multitargeting abilities and have been officially recommended for the management of COVID-19. Chinese herbal medicines have therapeutic actions promising for the treatment of sepsis; basic scientific research on these medicines is increasing. However, the material bases of most Chinese herbal medicines and their underlying mechanisms of action have not yet been fully elucidated. This review summarizes the current studies of Chinese herbal medicines used for the treatment of sepsis in terms of clinical efficacy and safety, pharmacological activity, phytochemistry, bioactive constituents, mechanisms of action, and pharmacokinetics, to provide an important foundation for clarifying the pathogenesis of sepsis and developing novel antisepsis drugs based on Chinese herbal medicines.

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Effect of Shenfu injection on intestinal mucosal barrier in a rat model of sepsis

Cited by 18 publications

References 24 publications

Curcumin Improved Intestinal Epithelial Barrier Integrity by Up-Regulating ZO-1/Occludin/Claudin-1 in Septic Rats

Curcumin Improved Intestinal Epithelial Barrier Integrity by Up-Regulating ZO-1/Occludin/Claudin-1 in Septic Rats

Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1

Research Progress in Chinese Herbal Medicines for Treatment of Sepsis: Pharmacological Action, Phytochemistry, and Pharmacokinetics

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